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Regulation of Food Intake01:30

Regulation of Food Intake

Short-term regulation of food intake primarily involves neural signals from the gastrointestinal (GI) tract, blood nutrient levels, and GI tract hormones. Communication between the gut and brain via vagal nerve fibers plays a significant role in evaluating the contents of the gut. Clinical studies have shown that protein ingestion produces a more prolonged response in these nerve fibers compared to an equivalent amount of glucose. Additionally, the activation of stretch receptors caused by GI...
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The action of leptin in the ventral tegmental area to decrease food intake is dependent on Jak-2 signaling.

Gregory J Morton1, James E Blevins, Francis Kim

  • 1Department of Medicine, University of Washington at South Lake Union, 815 Mercer St., Box 358055, Seattle, WA 98195, USA. gjmorton@u.washington.edu

American Journal of Physiology. Endocrinology and Metabolism
|May 14, 2009
PubMed
Summary

Leptin reduces food intake by acting in the brain's ventral tegmental area (VTA). This effect primarily uses Janus kinase-2 (Jak-2) signaling, unlike hypothalamic pathways.

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Area of Science:

  • Neuroscience
  • Endocrinology
  • Molecular Biology

Background:

  • Leptin is a key hormone regulating appetite and energy balance.
  • Leptin exerts anorectic effects through central nervous system pathways, including the ventral tegmental area (VTA).
  • Hypothalamic leptin signaling involves Janus kinase-signal transducer and activator of transcription (Jak-STAT), insulin receptor substrate (IRS)-phosphatidylinositol 3-kinase (PI 3-kinase), and mammalian target of rapamycin (mTOR) pathways.

Purpose of the Study:

  • To investigate leptin's activation of Jak-STAT, IRS-PI 3-kinase, and mTOR signaling pathways within the VTA.
  • To determine if these signaling pathways are essential for leptin-induced anorexia when administered directly to the VTA.

Main Methods:

  • Administered leptin intracerebroventricularly or directly into the VTA of rodents.
  • Measured levels of phosphorylated STAT3 (pSTAT3-Tyr705), phosphorylated AKT (pAKT-Ser473), and phosphorylated p70S6K (phospho-p70S6K-Thr389) as markers of pathway activation.
  • Utilized Jak-2, PI 3-kinase, and mTOR inhibitors locally in the VTA to assess pathway necessity for leptin's effects on food intake and body weight.

Main Results:

  • Leptin administration into the VTA induced pSTAT3-Tyr705, indicating Jak-STAT pathway activation.
  • Leptin did not increase levels of pAKT-Ser473 or phospho-p70S6K-Thr389, suggesting no activation of IRS-PI 3-kinase or mTOR signaling in the VTA.
  • Inhibition of Jak-2, but not PI 3-kinase or mTOR, blocked leptin's anorectic effects and body weight reduction in the VTA.

Conclusions:

  • Leptin signaling in the VTA contributes to the regulation of energy balance.
  • VTA-mediated leptin effects on food intake and body weight predominantly rely on Jak-2 signaling.
  • This contrasts with hypothalamic leptin signaling, which involves IRS-PI 3-kinase and mTOR pathways, highlighting distinct mechanisms in different brain regions.